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CGP3466B exerts its neuroprotective effect via inhibition of SNO-GAPDH formation. S-Nitrosylation of GAPDH enhances its interaction with Siah1 (bearing a nuclear localization signal) and promotes its translocation to the nucleus, whereas SNO-GAPDH triggers cellular events leading to neurodegeneration. CGP3466B (TCH346 or Omigapil) potently and selectively blocks GAPDH S-nitrosylation and thereby Siah binding.
